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EMC
/Span <>BDC
BT
0.138 Tw 10 0 0 10 36 403.152 Tm
[(although the latter is clearly of)25(f-label. )17.9(The)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.027 Tw 10 0 0 10 36 391.152 Tm
[(important )0.5(question )0.5(is, )0.5(then, )0.6(does )0.5(it )0.5(mak)10(e )0.5(an)15(y)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.025 Tw 10 0 0 10 36 379.152 Tm
[(dif)25(ference )]TJ
ET
EMC
/Span <>BDC
BT
/T1_4 1 Tf
10 0 0 10 75.7168 379.152 Tm
(when)Tj
ET
EMC
/Span <>BDC
BT
/T1_2 1 Tf
-0.031 Tw 10 0 0 10 95.8266 379.152 Tm
[( you gi)25(v)15(e insulin glar)18(gine, or)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0 Tw 10 0 0 10 36 367.152 Tm
(is it just personal preference?)Tj
ET
EMC
/Span <>BDC
BT
0.381 Tw 10 0 0 10 48.024 355.152 Tm
(The pharmacokinetics and pharmaco)Tj
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 198.6541 355.152 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.174 Tw 10 0 0 10 36 343.152 Tm
[(dynamics of insulin glar)18(gine were studied)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.026 Tw 10 0 0 10 36 331.152 Tm
[(in 10 subjects with type 2 diabetes who had)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.206 Tw 10 0 0 10 36 319.152 Tm
[(already been recei)25(ving insulin glar)18(gine as)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.167 Tw 10 0 0 10 36 307.152 Tm
[(part of their therapeutic re)15.1(gimen. Subjects)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.166 Tw 10 0 0 10 36 295.152 Tm
[(were randomized in a crosso)15(v)15(er design to)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.041 Tw 10 0 0 10 36 283.152 Tm
[(dose insulin glar)18(gine at either 10 a.m. or 10)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.173 Tw 10 0 0 10 36 271.152 Tm
(p.m., with dose optimization attained dur)Tj
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 198.6541 271.152 Tm
(-)Tj
ET
EMC
/GS0 gs
q 1 0 0 1 214.008 476.16 cm
0 0 m
165.984 0 l
S
Q
q 1 0 0 1 214.008 409.16 cm
0 0 m
165.984 0 l
S
Q
/Span <>BDC
BT
/GS1 gs
-0.025 Tc -0.011 Tw 10 0 0 10 214.008 748.16 Tm
[(ing a 2-week period to achie)25(v)15(e f)10.1(asting blood)-24.9( )]TJ
ET
EMC
/Span <>BDC
BT
0.068 Tw 10 0 0 10 214.008 736.16 Tm
[(glucose )0.5(\(FBG\) )]TJ
ET
EMC
/Span <>BDC
BT
/C2_2 1 Tf
0 Tc 0 Tw 10 0 0 10 273.5163 736.16 Tm
<0064>Tj
ET
EMC
/Span <>BDC
BT
/T1_2 1 Tf
-0.025 Tc 0.068 Tw 10 0 0 10 278.7545 736.16 Tm
[( )0.5(100 )0.5(mg/dL )0.6(without )0.5(e)15(xpe)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 376.662 736.16 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc -0.011 Tw 10 0 0 10 214.008 724.16 Tm
[(riencing nocturnal h)5(ypoglycemia \(glucose <)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0 Tw 10 0 0 10 214.008 712.16 Tm
(72 mg/dL\).)Tj
ET
EMC
/Span <>BDC
BT
0.285 Tw 10 0 0 10 226.032 700.16 Tm
[(Se)25(v)15(eral interesting results were noted.)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.06 Tw 10 0 0 10 214.008 688.16 Tm
[(First, the actual dose needed for optimization)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.096 Tw 10 0 0 10 214.008 676.16 Tm
[(of FBG w)10(as slightly greater when glar)18(gine)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.167 Tw 10 0 0 10 214.008 664.16 Tm
[(w)10(as administered at 10 a.m. than 10 p.m.)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.043 Tw 10 0 0 10 214.008 652.16 Tm
[(Second, morning administration of glar)18(gine)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.097 Tw 10 0 0 10 214.008 640.16 Tm
[(had )0.5(less )0.5(glucagon-suppression ef)25(fect )0.5(in )0.5(the)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.058 Tw 10 0 0 10 214.008 628.16 Tm
[(second )0.5(half )0.5(of )0.5(the 24-hr )0.5(c)15(ycle than )0.5(e)25(v)15(ening)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.085 Tw 10 0 0 10 214.008 616.16 Tm
[(administration )0.5(had )0.5(in )0.5(the )0.5(second )0.5(half )0.5(of )0.5(its)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.339 Tw 10 0 0 10 214.008 604.16 Tm
[(24-hr c)15(ycle. Ev)15(ening administration also)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.046 Tw 10 0 0 10 214.008 592.16 Tm
(limited lipolysis more than morning, result)Tj
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 376.662 592.16 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 10 0 0 10 214.008 580.16 Tm
[(ing in lo)25(wer le)25(v)15(els of plasma f)10(atty acids.)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.277 Tw 10 0 0 10 226.032 568.16 Tm
[(The dif)25.1(ferences between morning and)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.519 Tw 10 0 0 10 214.008 556.16 Tm
[(e)25(v)15(ening )0.5(glar)18(gine )0.5(administration )0.5(demon)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 376.662 556.16 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc -0.008 Tw 10 0 0 10 214.008 544.16 Tm
[(strated here are quite modest, b)20(ut do suggest)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.066 Tw 10 0 0 10 214.008 532.16 Tm
[(that o)15(v)15(erall, e)25(v)15(ening administration may be)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.011 Tw 10 0 0 10 214.008 520.16 Tm
[(superior )0.5(in )0.5(reference )0.5(to )0.5(some )0.5(dysre)15(gulations)-24.9( )]TJ
ET
EMC
/Span <>BDC
BT
0.173 Tw 10 0 0 10 214.008 508.16 Tm
[(seen in type 2 diabetes, such as glucagon)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0 Tw 10 0 0 10 214.008 496.16 Tm
[(and f)10.1(atty acids. )]TJ
ET
EMC
/Span <>BDC
BT
/CS0 cs 1 scn
/GS0 gs
/C2_1 1 Tf
0 Tc 10 0 0 10 275.2273 496.16 Tm
<0051>Tj
ET
EMC
/Span <>BDC
BT
0 0 0 1 k
/GS1 gs
/TT3 1 Tf
-0.025 Tc 14 0 0 14 214.008 462.16 Tm
[(Dual Add-on Therapy)-24.8( )]TJ
ET
EMC
/Span <>BDC
BT
14 0 0 14 214.008 446.16 Tm
[(for Type 2 Diabetes)-25( )]TJ
ET
EMC
/Span <>BDC
BT
14 0 0 14 214.008 430.16 Tm
[(When Metformin is Not)-24.8( )]TJ
ET
EMC
/Span <>BDC
BT
0.025 Tw 14 0 0 14 214.008 414.16 Tm
(Enough)Tj
ET
EMC
/Span <>BDC
BT
/T1_3 1 Tf
10 0 0 10 214.008 389.128 Tm
[(Sour)18(ce: )]TJ
ET
EMC
/Span <>BDC
BT
/T1_2 1 Tf
0.067 Tw 10 0 0 10 247.7686 389.128 Tm
(Rosenstock J, et al. )Tj
ET
EMC
/Span <>BDC
BT
/T1_4 1 Tf
10 0 0 10 324.6417 389.128 Tm
[(Diabetes Car)37(e)]TJ
ET
EMC
/Span <>BDC
BT
/T1_2 1 Tf
0 Tc 0 Tw 10 0 0 10 379.992 389.128 Tm
( )Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.025 Tw 10 0 0 10 214.008 377.128 Tm
(2015;38:376-383.)Tj
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 28.1269 0 0 28.1269 213.2301 347.152 Tm
(T)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.262 Tw 10 0 0 10 229.7123 359.152 Tm
[(he current \(2015\) )54.7(American Diabetes)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.005 Tw 10 0 0 10 229.7123 347.152 Tm
[(Association guidance for progression of)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.128 Tw 10 0 0 10 214.008 335.152 Tm
[(treatment when )54.9(A1c goals are not attained)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.156 Tw 10 0 0 10 214.008 323.152 Tm
[(with metformin implies stepwise initiation)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.177 Tw 10 0 0 10 214.008 311.152 Tm
[(of additional monotherapies. But w)10(ould it)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0 Tw 10 0 0 10 214.008 298.152 Tm
[(mak)10(e sense to consider dual add-on?)]TJ
ET
EMC
/Span <>BDC
BT
0.248 Tw 10 0 0 10 226.032 286.152 Tm
[(Rosenstock et al studied patients with)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.229 Tw 10 0 0 10 214.008 274.152 Tm
[(type 2 diabetes \(T2DM\) whose )54.7(A1c w)10(as)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.023 Tw 10 0 0 10 214.008 262.152 Tm
[(8.9% at baseline on monotherap)10(y with met)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 376.6621 262.152 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.21 Tw 10 0 0 10 214.008 250.152 Tm
[(formin. Subjects were randomized to add)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.189 Tw 10 0 0 10 214.008 238.152 Tm
[(a DPP4 inhibitor \(saxagliptin\), an SGL)92(T2)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.069 Tw 10 0 0 10 214.008 226.152 Tm
[(inhibitor \(Dapagli\036ozin\), or both, and were)-24.9( )]TJ
ET
EMC
/Span <>BDC
BT
0 Tw 10 0 0 10 214.008 214.152 Tm
[(follo)25(wed for 24 weeks.)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.258 Tw 10 0 0 10 226.032 202.152 Tm
[(All )0.6(three )0.5(re)15(gimens )0.6(were )0.6(successful )0.6(to)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.133 Tw 10 0 0 10 214.008 190.152 Tm
[(reduce )55.2(A1c from baseline, and it probably)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.022 Tw 10 0 0 10 214.008 178.152 Tm
[(comes as no surprise that the addition of tw)10(o)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.178 Tw 10 0 0 10 214.008 166.152 Tm
(drugs \(DPP4 inhibitor )Tj
ET
EMC
/Span <>BDC
BT
/T1_4 1 Tf
0.025 Tw 10 0 0 10 304.6844 166.152 Tm
(and)Tj
ET
EMC
/Span <>BDC
BT
/T1_2 1 Tf
0.178 Tw 10 0 0 10 318.9344 166.152 Tm
[( SGL)92(T2 inhibi)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 376.6621 166.152 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.002 Tw 10 0 0 10 214.008 154.152 Tm
[(tor\) to metformin outperformed the addition)-24.9( )]TJ
ET
EMC
/Span <>BDC
BT
0.157 Tw 10 0 0 10 214.008 142.152 Tm
[(of either monotherap)10(y)64.9(. )17.5(The addition of an)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.014 Tw 10 0 0 10 214.008 130.152 Tm
[(SGL)92(T2 to metformin demonstrated substan)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 376.6621 130.152 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc -0.018 Tw 10 0 0 10 214.008 118.152 Tm
[(tially better )55.1(A1c reductions than the addition)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.06 Tw 10 0 0 10 214.008 106.152 Tm
[(of a DPP4 inhibitor \(-0.9% vs -0.59%\), b)20(ut)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.008 Tw 10 0 0 10 214.008 94.152 Tm
[(the three-drug combination w)10(as f)10(ar more ef)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 376.6621 94.152 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 10 0 0 10 214.008 82.152 Tm
[(fecti)25(v)15(e, pro)15(viding a -1.5% )55(A1c reduction.)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.083 Tw 10 0 0 10 226.032 70.152 Tm
[(The simultaneous addition of tw)10(o drugs)-25( )]TJ
ET
EMC
/GS0 gs
q 1 0 0 1 392.016 559.08 cm
0 0 m
165.984 0 l
S
Q
q 1 0 0 1 392.016 508.08 cm
0 0 m
165.984 0 l
S
Q
/Span <>BDC
BT
/GS1 gs
0.173 Tw 10 0 0 10 392.016 747.08 Tm
[(to metformin monotherap)10(y is probably an)-24.9( )]TJ
ET
EMC
/Span <>BDC
BT
-0.039 Tw 10 0 0 10 392.016 735.08 Tm
[(uncommon step for clinicians, who are more)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.02 Tw 10 0 0 10 392.016 723.08 Tm
[(accustomed )0.5(to )0.5(progressi)25(v)15(e )0.5(monotherapeutic)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.03 Tw 10 0 0 10 392.016 711.08 Tm
[(step adv)25(ancements. )18(The f)10(act that there were)-24.9( )]TJ
ET
EMC
/Span <>BDC
BT
0.088 Tw 10 0 0 10 392.016 699.08 Tm
[(no episodes of major h)5(ypoglycemia during)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.133 Tw 10 0 0 10 392.016 687.08 Tm
[(the 6 months of the trial is reassuring that)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.039 Tw 10 0 0 10 392.016 675.08 Tm
[(similar therapeutic steps may be safely tak)10(en)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.085 Tw 10 0 0 10 392.016 663.08 Tm
[(in practice settings where patients continue)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.066 Tw 10 0 0 10 392.016 651.08 Tm
[(to ha)20(v)15(e an ele)25(v)25(ated )54.6(A1c on metformin. Be)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 554.67 651.08 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc -0.04 Tw 10 0 0 10 392.016 639.08 Tm
[(cause of the v)15(ery potent )55.3(A1c reduction, ho)25(w)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 554.67 639.08 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc -0.013 Tw 10 0 0 10 392.016 627.08 Tm
[(e)25(v)15(er)40(, it is equally important to select patients)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.088 Tw 10 0 0 10 392.016 615.08 Tm
[(with a suf\037ciently ele)25(v)25(ated )54.7(A1c on metfor)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 554.67 615.08 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.133 Tw 10 0 0 10 392.016 603.08 Tm
[(min \(at least 8.9%\) so that the addition of)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.01 Tw 10 0 0 10 392.016 591.08 Tm
[(dual )0.6(add-on )0.5(treatment )0.5(does )0.5(not )0.5(lead )0.6(to )0.5(prob)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 554.67 591.08 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 10 0 0 10 392.016 579.08 Tm
[(lematic h)5(ypoglycemia. )]TJ
ET
EMC
/Span <>BDC
BT
/CS0 cs 1 scn
/GS0 gs
/C2_1 1 Tf
0 Tc 10 0 0 10 482.3152 579.08 Tm
<0051>Tj
ET
EMC
/Span <>BDC
BT
0 0 0 1 k
/GS1 gs
/TT3 1 Tf
-0.025 Tc 14 0 0 14 392.016 545.08 Tm
[(Might Long-term Dual)-25.1( )]TJ
ET
EMC
/Span <>BDC
BT
14 0 0 14 392.016 529.08 Tm
[(Antiplatelet Therapy)-24.8( )]TJ
ET
EMC
/Span <>BDC
BT
14 0 0 14 392.016 513.08 Tm
(Be Better? Not)Tj
ET
EMC
/Span <>BDC
BT
/T1_3 1 Tf
0.025 Tw 10 0 0 10 392.016 488.048 Tm
[(Sour)18(ce: )]TJ
ET
EMC
/Span <>BDC
BT
/T1_2 1 Tf
0.271 Tw 10 0 0 10 427.8115 488.048 Tm
(Elmariah S, et al. )Tj
ET
EMC
/Span <>BDC
BT
/T1_4 1 Tf
0.025 Tw 10 0 0 10 505.5444 488.048 Tm
(Lancet )Tj
ET
EMC
/Span <>BDC
BT
/T1_2 1 Tf
10 0 0 10 536.22 488.048 Tm
(2014;)Tj
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 558 488.048 Tm
( )Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.025 Tw 10 0 0 10 392.016 476.048 Tm
(385:792-98)Tj
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 28.1269 0 0 28.1269 391.4798 446.072 Tm
(R)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc -0.077 Tw 10 0 0 10 409.537 458.072 Tm
[(isk reduction pro)15(vided by dual antiplate)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 554.67 458.072 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.077 Tw 10 0 0 10 409.537 446.072 Tm
[(let therap)10(y \(D)40.1(A)111(T\) in the short-term in)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 554.67 446.072 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.035 Tw 10 0 0 10 392.016 434.072 Tm
[(terv)25(al \(3-12 months\) after coronary stenting)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.016 Tw 10 0 0 10 392.016 422.072 Tm
[(is well established, and published guidelines)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.056 Tw 10 0 0 10 392.016 410.072 Tm
[(pro)15(vide consistent advice about appropriate)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.116 Tw 10 0 0 10 392.016 398.072 Tm
[(duration of such therap)10(y)65(. In essentially e)25(v)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 554.67 398.072 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc -0.032 Tw 10 0 0 10 392.016 386.072 Tm
[(ery lar)18.1(ge randomized trial that has compared)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.101 Tw 10 0 0 10 392.016 374.072 Tm
[(D)40(A)111(T to monotherap)10(y)65(, bleeding risks go up)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.138 Tw 10 0 0 10 392.016 362.072 Tm
[(to a suf\037cient le)25(v)15(el that it counterbalances)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.015 Tw 10 0 0 10 392.016 350.072 Tm
[(an)15(y risk reduction in reference to cardio)15(v)25(as)]TJ
ET
EMC
/Span <>BDC
BT
0 Tc 0 Tw 10 0 0 10 554.67 350.072 Tm
(-)Tj
ET
EMC
/Span <>BDC
BT
-0.025 Tc 0.072 Tw 10 0 0 10 392.016 338.072 Tm
[(cular e)25(v)15(ents. Indeed, tw)10(o major me)15(g)5(a-trials)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.187 Tw 10 0 0 10 392.016 326.072 Tm
[(comparing D)40(A)111(T to monotherap)10(y in stable)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.274 Tw 10 0 0 10 392.016 314.072 Tm
[(patients with established v)25.1(ascular disease)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.01 Tw 10 0 0 10 392.016 302.072 Tm
[(f)10(ailed to demonstrate )0.5(bene\037cial reduction )0.5(in)-25( )]TJ
ET
EMC
/Span <>BDC
BT
-0.001 Tw 10 0 0 10 392.016 290.072 Tm
[(strok)10(e \(the MA)111(TCH trial\) or stable coronary)-25( )]TJ
ET
EMC
/Span <>BDC
BT
0.015 Tw 10 0 0 10 392.016 278.072 Tm
[(disease \(the CHARISMA trial\), b)20(ut did \037nd)-25( )]TJ
ET
EMC
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BT
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